Advances and prospects of 3D air-liquid interface cultured middle ear epithelial cells and inner ear organoids in otologic diseases.

Hearing loss and vestibular disorders represent major otologic disease challenges. Traditional disease models struggle to accurately mimic human otologic pathologies due to species differences and limited physiological relevance. Recent advancements in otic vitro models have provided crucial tools for related research. The core representatives include the middle ear epithelial cell model cultured at the air-liquid interface (ALI) and inner ear organoids. ALI culture of middle ear epithelial cells highly mimics middle ear tissue structure and function, finding applications in drug screening and toxicity assessment. Inner ear organoids facilitate the in vitro generation of functional three-dimensional structures containing hair cells, supporting cells, and neurons, while recapitulating both inner ear development and specific disease phenotypes. This review highlights the origins, research progress, and application prospects of these two model types, aiming to provide references for elucidating otologic disease mechanisms, personalized drug screening, and evaluating gene therapy strategies.